The major objectives of this request are to develop and expand chemical carcinogenesis regimen which will make easier the analysis of macromolecular interactions and cellular events in the evolution to malignancy. It has been reported that a single administration of 3 chemical agents during liver regeneration ill result in production of hepatoma(s). We will greatly expand this approach by examining the effect of a single-exposure of carcinogens from 4 major chemical calsses administered at 5 points of cellular alteration during the highly synchronous regenerative cycle of the weanling rat. Previous studies used the much less synchronous adult response. In addition, the effects of secondary challenges which have been hypothesized as participating in the sequences of malignant transformation such as mitotic activity, free radical generation, necrosis and mitosis, etc, will be examined. Lastly, a unique system for testing carcinogens and analyzing their intracellular effects has been developed in our lab- the use of oocytes of xenopus laevis. These can be expected at one phase of cell cycle; development and metamorphic evolution. Single cells or any number of cells can be thus exposed.